If we prevent bacteria in urine (bacteriuria), could we decrease lupus flares?
Bacteria in urine was found in a study to possibly increase flares in lupus patients. If this is true, then decreasing bacteria in the urine could possibly help lower the risk of lupus flare is people who have systemic lupus erythematosus (SLE).
Bacteria in urine is a common problem in women, so this could be an important problem to address.
Background for this study
– Could bacteria in urine cause lupus flares? Bacteria such as E. coli can infect the urinary tract, such as the bladder. They can produce proteins called “amyloid curli” that can trigger the immune system to become more active. Part of this is through something called “toll-like receptors,” a well-known trigger of increased lupus activity.
(Off topic, Plaquenil, our most important drug for lupus inhibits toll-like receptors- one way it works for lupus).
– This bacterial amyloid curli is connected to something called extracellular DNA (DNA from the bacteria that sits on the outside of the cell).
Remember, that anti-dsDNA antibodies are very important in lupus disease activity.
– This bacterial DNA can “mimic” human DNA and potentially trigger the immune system to make autoantibodies to anti-dsDNA, like we see in lupus!
– Research studies showed that when this amyloid curli bound to extracellular DNA (from bacteria) is injected into mice that are genetically predisposed to having lupus, they develop systemic lupus quicker and more often.
Background of bacteria in urine of women who have lupus
Women who have lupus commonly have bacteria in their urine. This is partly due to the urethra of women being so short. This allows bacteria from the vagina and vulva to enter the bladder easier. This is common in all women. Most of the time, these bacteria do not cause infection (urinary tract infection, UTI).
We get a urine sample from our patients with systemic lupus erythematosus (SLE) every 3 months to make sure they do not have inflammation of the kidneys (lupus nephritis). Many times there are bacteria in the urine when we analyze it.
One of the most common phone calls my medical assistant makes for me is calling up my SLE patients and asking, “are you having any UTI symptoms?” Usually they say “no,” in which case we call it “asymptomatic bacteriuria” (there is bacteria in the urine but the person does not have any symptoms of a UTI).
The standard of medical care is to NOT treat it with antibiotics. Asymptomatic bacteriuria usually does not cause problems. However, an antibiotic has a high risk for side effects (stomach upset, allergic reaction, rash, yeast infection, and so on). So, instead, we ask our patients to drink cranberry juice daily, take a cranberry supplement, and/or take D-Mannose daily. This is based on research where 13 studies with 1616 subjects demonstrated that taking daily cranberry reduced UTIs by approximately 40%. Studies also show that cranberry decreases the ability of urinary bacteria to stick to the walls of the bladder and urethra.
In the past, I always told my patients, “this is common because of your short urethra and is nothing to worry about.”
THIS STUDY WILL CHANGE MY MIND AND WHAT I TELL MY PATIENTS… READ ON…
Photo above is one possible type of supplement that may decrease the risk of UTIs when taken daily. It contains both cranberry and D-mannose. I am not advocating this particular brand, it is just an example.
These researchers measured antibodies to these bacteria proteins bound to DNA and they showed:
– 1/3 of SLE women have persistent bacteria in the urine!
– These lupus patients tend to have more active lupus disease than those women without bacteria in the urine
– They were also more likely to have high anti-dsDNA levels and low C3 and C4 complement levels (indicators of active lupus inflammation)
– They also had higher levels of antibodies to this amyloid curli/DNA complexes
– These curli/DNA complexes from the urinary bacteria cross-reacted with lupus autoantigen dsDNA! (suggesting something called molecular mimicry)
MAJOR FINDING: The urinary bacteria’s curli/DNA proteins triggered increased lupus inflammation and lupus flares in women with SLE!
A summary of this research in the highly acclaimed medical journal “Arthritis & Rheumatology” summarized:
“Lupus patients with persistent bacteriuria could be targeted with appropriate antibiotic therapy as adjunct to standard of care.”
HOW THIS WILL CHANGE MY PRACTICE:
I will not start treating all my SLE patients with asymptomatic bacteriuria with antibiotics. The potential risks of side effects from the antibiotics outweigh the potential benefits. I will await the next-step research where someone does a research study treating SLE patients like this with antibiotics and see what happens. However, what I will do…
In SLE patients who have bacteria in their urine (bacteriuria), I will recommend that they consider taking a cranberry supplement and/or D-Mannose supplement daily and stay on it. It is such a safe thing to do with potential significant benefits.
Fascinating study that has the potential for significant positive benefits for our patients. Thank you to the dedicated researchers of Ryan Pachucki, MS, and Roberto Caricchio, MD and their entire team!
Do you get frequent urinary tract infections? Do you notice any relationship to lupus flares? Please comment and share your experience
SHARE THIS IMPORTANT, PRACTICAL POST WITH EVERYONE YOU KNOW WHO HAS LUPUS!
– Wang CH et al. Cranberry-containing products for prevention of urinary tract infections in susceptible populations: a systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2012;172(13):988.
– Kranjčec B, Papeš D, Altarac S. D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J Urol. 2014 Feb;32(1):79-84. doi: 10.1007/s00345-013-1091-6. Epub 2013 Apr 30. PMID: 23633128.
– Pachucki RJ, Corradetti C, Kohler L, Ghadiali J, Gallo PM, Nicastro L, Tursi SA, Gallucci S, Tükel Ç, Caricchio R. Persistent Bacteriuria and Antibodies Recognizing Curli/eDNA Complexes From Escherichia coli Are Linked to Flares in Systemic Lupus Erythematosus. Arthritis Rheumatol. 2020 Jun 17. doi: 10.1002/art.41400. Epub ahead of print. PMID: 32840064.